- Preclinical Data Highlights BLU-5937 as a Potential Best-In-Class Treatment for Chronic Cough -- First In-Human Study to Begin in July 2018 -

LAVAL, QC, June 27, 2018 /CNW/ - BELLUS Health Inc. (TSX: BLU) ("BELLUS Health" or the "Company"), a biopharmaceutical development company advancing novel therapeutics for conditions with high unmet medical need, today presented preclinical data on its lead drug candidate, BLU-5937 for the treatment of chronic cough. Dr. Denis Garceau, BELLUS Health's Senior Vice President, Drug Development, provided a review of the data at the 2018 International Cough Symposium in London, UK. In summary, animal studies demonstrated that BLU-5937 is a highly selective P2X3 antagonist exhibiting a potent anti-tussive effect without affecting taste perception. The preclinical toxicology studies also demonstrated an excellent safety profile for BLU-5937.

The Company also updated the timeline for the initiation of its first in-human study for BLU-5937 to July 2018. The main objectives of the Phase 1 clinical study will be to assess the safety, tolerability (including taste perception) and pharmacokinetic profile of BLU-5937 in healthy subjects.

"The results of our preclinical studies demonstrate that BLU-5937 selectively targets the receptors that have been shown to play a major role in the cough reflex, leading to a significant reduction in cough frequency without affecting taste," said Dr. Denis Garceau, Senior Vice President of BELLUS Health. "We are poised to begin in the coming weeks our first in-human study for BLU-5937 and are looking forward to reporting the results in the fourth quarter of 2018."

Highlights of the Presentation

P2X3 receptors are known to assemble and function as P2X3 homotrimer or P2X2/3 heterotrimer structures. Histological, immunochemistry and behavioral taste studies performed in rodents suggest that P2X3 receptors are involved in cough reflex hypersensitivity, while P2X2/3 receptors play a major role in taste function.

Preclinical data gathered to date have revealed that BLU-5937 is a highly selective antagonist of P2X3 homotrimeric receptors that can reduce cough without affecting taste perception.

BELLUS Health's hypothesis is that a drug that selectively inhibits P2X3 homotrimeric receptors would have the potential to reduce cough without affecting taste function. To test this hypothesis a series of experiments were performed with BLU-5937:

In a cell-based assay, BLU-5937 was shown to be 2,000 times more selective for human P2X3 homotrimeric receptors than for human P2X2/3 heterotrimeric receptors.

In isolated sensory neurons expressing P2X3 receptors, BLU-5937 was able to block the ATP-mediated sensitization of the fibres.

The anti-tussive effect of BLU-5937 was assessed in a guinea pig cough model, in which the animals were exposed to citric acid and histamine or ATP to induce cough. BLU-5937 significantly and dose-dependently reduced cough frequency compared to control animals. The efficacy of BLU-5937 was comparable to that of a potent, non-selective P2X3 antagonist, NEO588 (gefapixant).

The analysis of BLU-5937 blood levels revealed that the anti-tussive effect was obtained at concentrations known to block P2X3 receptors, but lower than that required to inhibit P2X2/3 receptors. These results indicate that the anti-tussive effect of BLU-5937 was mediated through the inhibition of P2X3 homotrimeric receptors.

The effect of BLU-5937 on taste perception was compared to NEO588, a potent, non-selective P2X3 antagonist, in a rat behavioral taste model. In this study, BLU-5937 did not alter taste perception as compared to control animals. In the same experiment, NE0588 had a significant inhibitory effect on taste perception.

While a drug that inhibits both receptors (P2X3 and P2X2/3) is known to cause taste alteration or taste loss, these results support the hypothesis that a drug that inhibits P2X3 receptors exclusively could have low or no effect on taste

The preclinical toxicology and pharmacokinetic program supporting the clinical Phase 1 study has been completed and revealed that BLU-5937 exhibits drug-like characteristics, such as very good oral absorption and tolerability, with a predicted twice daily dosing regimen.

A clinical Phase 1 study will be conducted in healthy subjects and will be divided in two parts: a single ascending dose including 6 cohorts of 10 subjects and a multiple ascending dose with 3 cohorts of 10 subjects to be dosed for 7 consecutive days. The Phase 1 study is expected to start in July 2018, with results expected in the fourth quarter of 2018.

A Phase 2 proof-of-concept study is expected to be initiated in 2019 in chronic cough patients. The dose escalation study will assess the safety, tolerability and efficacy of BLU-5937.

BELLUS Health is a biopharmaceutical development company advancing novel therapeutics for conditions with high unmet medical need. Its pipeline of projects includes the Company's lead drug candidate BLU-5937 for chronic cough and several other partnered clinical-stage drug development programs. BLU-5937, a selective P2X3 antagonist, has the potential to be a best-in-class therapeutic for chronic cough patients who do not respond to current therapies.

Chronic cough is a cough that lasts more than eight weeks and is associated with significant adverse social, psychosocial and physical effects on quality of life. A recent commercial assessment performed by Torreya Insights on behalf of the Company concluded that, in the United States alone, more than 26 million adults have chronic cough and more than 2.6 million of these patients suffer from refractory chronic cough lasting for more than a year.

Forward-Looking Statements

Certain statements contained in this news release, other than statements of fact that are independently verifiable at the date hereof, may constitute "forward-looking statements" within the meaning of Canadian securities legislation and regulations. Such statements, based as they are on the current expectations of management, inherently involve numerous important risks, uncertainties and assumptions, known and unknown, many of which are beyond BELLUS Health Inc.'s control. Such risks factors include but are not limited to: the ability to expand and develop its project pipeline, the ability to obtain financing, the impact of general economic conditions, general conditions in the pharmaceutical industry, changes in the regulatory environment in the jurisdictions in which BELLUS Health Inc. does business, stock market volatility, fluctuations in costs, changes to the competitive environment due to consolidation, achievement of forecasted burn rate, potential payments/outcomes in relation to indemnity agreements and contingent value rights, achievement of forecasted pre-clinical and clinical trial milestones and that actual results may vary once the final and quality-controlled verification of data and analyses has been completed. In addition, the length of BELLUS Health Inc.'s drug candidates' development process, their market size and commercial value, as well as the sharing of proceeds between BELLUS Health Inc. and its potential partners from potential future revenues, if any, are dependent upon a number of factors. Consequently, actual future results and events may differ materially from the anticipated results and events expressed in the forward-looking statements. BELLUS Health Inc. believes that expectations represented by forward-looking statements are reasonable, yet there can be no assurance that such expectations will prove to be correct. The reader should not place undue reliance, if any, on any forward-looking statements included in this news release. These forward-looking statements speak only as of the date made, and BELLUS Health Inc. is under no obligation and disavows any intention to update publicly or revise such statements as a result of any new information, future event, circumstances or otherwise, unless required by applicable legislation or regulation. Please see BELLUS Health Inc.'s public filings with the Canadian securities regulatory authorities, including the Annual Information Form, for further risk factors that might affect BELLUS Health Inc. and its business.